medchem 19

Question 1

to inhibit an enzyme we introduce a drug to the —- to bind — and —- and they usually react with —- and form —-
amino acids such as serine contains —-

Answer 1

• active site to bind irreversibly with it and blocks it permemntatlu
• amino acids and forms covelent bonds
• reactive 0h commonly present in enexzyme reactive site

Question 2

the mode of action of aspirin isinhibiting —– and it reacts with —–

Answer 2

• inhibits PGH2 or COX aka cycloocygenase
• serine residue in the active site which has OH

Question 3

ester ( aspirin ) + alcohol ( serine ) –> inhibited enzyme + phenol ( salicylic acid )

Answer 3

inhibited enzyme + phenol ( salicylic acid )

Question 4

mode of action of the penicillin

Answer 4

inhibits glycopeptiode transpeptidase and it reacts with serine residue in the active site of the enzyme

Question 5

lactam - cylic amid (penicillin ) + serine (oh) —>

Answer 5

inhibited enzyeme aka ester + amine

Question 6

aspirin inhibits the enzyme called — this enzyme converts —-
( that’s how aspirin is an anti-inflammatory, anti - pyretic and analgesic agents )

Answer 6

prostaglandin -h2- sythesase or cylcoxyogenase ( COX)
converts archodonic acid into prostaglandin and thromoboxanes

Question 7

prostaglandin is a hormone reposinble for

Answer 7

fever,pain, and inflammatory responses and has low concentrations so aspirin will relieve these symptoms

Question 8

the side effects of the aspirin:

Answer 8

irritation for the gastric mucosa and the nephrotoxixty aka the alteration of salt and water in the kidney

Question 9

prostaglandins are made up of —- with the enzyme —- being the catalyst

Answer 9

arachidonic acid , pgh2

Question 10

aspirin is an example of

Answer 10

NSAIDS : non steroid anti inflammatory drug which inhibits he cox

Question 11

the interaction of arachondic acid with cox

Answer 11

arachidonic acid ( sign is -ve )will enter the cox active site and will bind to agginine ( which is +ve) 119 to form salt bridges through the carboxylate group which will then be converted to prostogaldin

Question 12

how does aspirin inhibits cox ?

Answer 12

acetyl grou ( ch3c0 ) of aspirin will be transferred to alcohol group of the enzyme in the nucleophilic susbution reaction leaving the enzyme inhibited

Question 13

aspirin inhibition summary
( CHECK THE MECHANISM AND CHECK SLIDE 13)

Answer 13

• the aspirin inhibits cox by binding to arginine 119 ( in the electrostatic interactions )
• transfers the acetyl group to serine residue near the entrance of the active site
• the acetylation is irreversible and prevents the entry of arachodnic acid by the steric effects

Question 14

the two types of cox

Answer 14

• COX-1 : housekeeping enzyme reposible for the protection of gastric, vacuslar , Renal and inhibition of the COX 1 leads to their toxicity and the adverse side effect is their damage to the kidney and gastric mucosa
• C0X 2: responds to the stimuli and inhibition of it leads to anti-inflammatory, analgestic and anti pyretic effects and its reposnisbel for mediate inflammation pain and fever. it’s the therapeutic effects of aspirin . Selective COX 2 inhibitor should have the therapeutic effects but not the side effects of aspirin

Question 15

the difference between cox 1 and cox 2

Answer 15

• the difference is the cox active site in position 523
• cox 1 is isoleucine IIe 523 , slightly bigger
• cox 2 is valine 523 , and has one less ch2 so it has slightly bigger binding pocket

Question 16

celecoxib is selective inhibitor for —

Answer 16

• cox 2
• the celecoxib fits into the active site region of cox 2 as the sulfoamide group fits into the side pocket and prevents the entry of arachondic acid.
• it causes less ulceration in the stomach and intestine than other NSAIDS
  -doesnt work w/ COX 1 because sulfoamide can’t be accomdated due to the sterically bulkier isoleucine amino acid so arachnid acid can enter unimpeded .

Question 17

penicillin stucture:
penicillin properties:

Answer 17

• contains cyclic amid lactam and its b lactam because it has two additional carbons in the amide/lactam ring.
• it also has sulphur in the five membered ring
• b- lactam ring is strained making it reactive and liable bond between the carbonyl group and nitrogen
• bicyclic system has a well defined shape and a half open book shape, it mimic the topology of the enzyme bc of its well defined shape
• its not a planer so it makes it more stable and resonances is reduced

Question 18

penicillin leads to inactive —- which inhibits the —-

Answer 18

• glycopeptide transpeptidase
• cell wall biosynthesis

Question 19

the reason why lactam ( amide ) + alcohol –> amine + ester can occur:

Answer 19

• the structure of penicillin has lactam with different structure from amides
• resonance is reduced and the carbonyl in the b lactam becomes more like keton and less like amide
• and the reactivity of the b lactam towards nucleophiles is more than amides
• its not a planer structure ( 2 fused rings lie at an angle )because of the excessive ring strain ( the bond angles are smaller than 109 )

Question 20

the last step of the action of reaction mechanism of penicillin with GPTase is

Answer 20

release of the ring strain
( CHECK THE MEHCANISM )